Does p. Q247X in TRIM63 Cause Human Hypertrophic Cardiomyopathy?

被引：81

作者：

Ploski, Rafal ^{[1
]}

Pollak, Agnieszka ^{[3
]}

Mueller, Sonja ^{[4
]}

Franaszczyk, Maria ^{[5
]}

Michalak, Ewa ^{[6
]}

Kosinska, Joanna ^{[1
]}

Stawinski, Piotr ^{[2
]}

Spiewak, Mateusz ^{[7
]}

Seggewiss, Hubert ^{[4
]}

Bilinska, Zofia T. ^{[6
]}

机构：

[1] Med Univ Warsaw, Dept Med Genet, Ctr Biostruct Res, Warsaw, Poland

[2] Med Univ Warsaw, Dept Immunol, Ctr Biostruct Res, Warsaw, Poland

[3] Inst Physiol & Pathol Hearing, Warsaw, Poland

[4] Leopoldina Krankenhaus, Med Klin 1, Schweinfurt, Germany

[5] Inst Cardiol, Mol Biol Lab, PL-04628 Warsaw, Poland

[6] Inst Cardiol, Unit Screening Studies Inherited Cardiovasc Dis, PL-04628 Warsaw, Poland

[7] Inst Cardiol, Cardiac Magnet Resonance Unit, PL-04628 Warsaw, Poland

来源：

CIRCULATION RESEARCH | 2014年 / 114卷 / 02期

关键词：

cardiomyopathy; hypertrophic; TRIM63; protein; human; DNA-SEQUENCING DATA; GENETIC-VARIANTS; MUTATIONS; FRAMEWORK;

D O I：

10.1161/CIRCRESAHA.114.302662

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Rationale: Variants in TRIM63, including a nonsense mutation (p.Q247X), have been suggested recently to cause hypertrophic cardiomyopathy. Objective: To verify pathogenicity of TRIM63 p.Q247X detected by whole-exome sequencing in a symptomless professional sports player seeking medical advice because of a prolonged QT interval found during a routine check-up. Methods and Results: Clinical studies were performed in the proband and his mother, who also carried TRIM63 p.Q247X. No evidence of hypertrophic cardiomyopathy was found in either person. Conclusions: The p.Q247X variant in TRIM63 is not likely to be a highly penetrant variant causing hypertrophic cardiomyopathy.

引用

页码：E2 / E5

页数：4

共 14 条

[1] Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia [J].

Bauce, Barbara ;

Nava, Andrea ;

Beffagna, Giorgia ;

Basso, Cristina ;

Lorenzon, Alessandra ;

Smaniotto, Gessica ;

De Bortoli, Marzia ;

Rigato, Ilaria ;

Mazzotti, Elisa ;

Steriotis, Alexandros ;

Marra, Martina Perazzolo ;

Towbin, Jeffry A. ;

Thiene, Gaetano ;

Danieli, Gian Antonio ;

Rampazzo, Alessandra .

HEART RHYTHM, 2010, 7 (01) :22-29

[2] Human Molecular Genetic and Functional Studies Identify TRIM63, Encoding Muscle RING Finger Protein 1, as a Novel Gene for Human Hypertrophic Cardiomyopathy [J].

Chen, Suet Nee ;

Czernuszewicz, Grazyna ;

Tan, Yanli ;

Lombardi, Raffaella ;

Jin, Jianping ;

Willerson, James T. ;

Marian, Ali J. .

CIRCULATION RESEARCH, 2012, 111 (07) :907-+

[3] A framework for variation discovery and genotyping using next-generation DNA sequencing data [J].

DePristo, Mark A. ;

Banks, Eric ;

Poplin, Ryan ;

Garimella, Kiran V. ;

Maguire, Jared R. ;

Hartl, Christopher ;

Philippakis, Anthony A. ;

del Angel, Guillermo ;

Rivas, Manuel A. ;

Hanna, Matt ;

McKenna, Aaron ;

Fennell, Tim J. ;

Kernytsky, Andrew M. ;

Sivachenko, Andrey Y. ;

Cibulskis, Kristian ;

Gabriel, Stacey B. ;

Altshuler, David ;

Daly, Mark J. .

NATURE GENETICS, 2011, 43 (05) :491-+

[4] In Vitro Functional Analyses of Arrhythmogenic Right Ventricular Cardiomyopathy-Associated Desmoglein-2-Missense Variations [J].

Gaertner, Anna ;

Klauke, Baerbel ;

Stork, Ines ;

Niehaus, Karsten ;

Niemann, Gesa ;

Gummert, Jan ;

Milting, Hendrik .

PLOS ONE, 2012, 7 (10)

[5] Desmosomal protein gene mutations in patients with idiopathic dilated cardiomyopathy undergoing cardiac transplantation: a clinicopathological study [J].

Garcia-Pavia, Pablo ;

Syrris, Petros ;

Salas, Clara ;

Evans, Alison ;

Mirelis, Jesus G. ;

Cobo-Marcos, Marta ;

Vilches, Carlos ;

Bornstein, Belen ;

Segovia, Javier ;

Alonso-Pulpon, Luis ;

Elliott, Perry M. .

HEART, 2011, 97 (21) :1744-1752

[6] Fast and accurate short read alignment with Burrows-Wheeler transform [J].

Li, Heng ;

Durbin, Richard .

BIOINFORMATICS, 2009, 25 (14) :1754-1760

[7] Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia Proposed Modification of the Task Force Criteria [J].

Marcus, Frank I. ;

McKenna, William J. ;

Sherrill, Duane ;

Basso, Cristina ;

Bauce, Barbara ;

Bluemke, David A. ;

Calkins, Hugh ;

Corrado, Domenico ;

Cox, Moniek G. P. J. ;

Daubert, James P. ;

Fontaine, Guy ;

Gear, Kathleen ;

Hauer, Richard ;

Nava, Andrea ;

Picard, Michael H. ;

Protonotarios, Nikos ;

Saffitz, Jeffrey E. ;

Sanborn, Danita M. Yoerger ;

Steinberg, Jonathan S. ;

Tandri, Harikrishna ;

Thiene, Gaetano ;

Towbin, Jeffrey A. ;

Tsatsopoulou, Adalena ;

Wichter, Thomas ;

Zareba, Wojciech .

CIRCULATION, 2010, 121 (13) :1533-U118

[8] The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data [J].

McKenna, Aaron ;

Hanna, Matthew ;

Banks, Eric ;

Sivachenko, Andrey ;

Cibulskis, Kristian ;

Kernytsky, Andrew ;

Garimella, Kiran ;

Altshuler, David ;

Gabriel, Stacey ;

Daly, Mark ;

DePristo, Mark A. .

GENOME RESEARCH, 2010, 20 (09) :1297-1303

[9]

NHLBI Exome Sequencing Project, EX VAR SERV NHLBI GO

[10] Integrative genomics viewer [J].

Robinson, James T. ;

Thorvaldsdottir, Helga ;

Winckler, Wendy ;

Guttman, Mitchell ;

Lander, Eric S. ;

Getz, Gad ;

Mesirov, Jill P. .

NATURE BIOTECHNOLOGY, 2011, 29 (01) :24-26

← 1 2 →